Journal Club 2015.06.12.

RESEARCH ARTICLE

Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa

journal.pone.0127060

Hana Moon1☯, Min Jung Kim1☯, Hee Jin Son1, Hae-Jin Kweon2, Jung Tae Kim1, Yiseul Kim1, Jaewon Shim1, Byung-Chang Suh2, Mee-Ra Rhyu1*
1 Research Group of Food Functionality, Korea Food Research Institute, Bundang-gu, Sungnam-si, Gyeonggi-do, Republic of Korea, 2 Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea
☯ These authors contributed equally to this work. * mrrhyu@kfri.re.kr

Abstract
Transient receptor potential ankyrin1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syr- ingate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer) O. Kuntze (A.rugosa), commonly known as Korean mint to improve hTRPA1-related phenome- na. An extract of the stem and leaves of A.rugosa (Labiatae) selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β- caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and ros- marinic acid) on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisal- dehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2 ±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Al- though the five active compounds showed weaker calcium responses than allyl isothiocya- nate (EC50=7.2±1.4 μM), our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1.